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Journal of Applied Toxicology

Characterization of the biochemical effects of naphthalene on the mouse respiratory system using NMR-based metabolomics

Authors

  • Jia-Huei Hong,

    1. Institute of Environmental Health, College of Public Health, National Taiwan University, Taipei, Taiwan, Republic of China
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  • Wen-Ching Lee,

    1. Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
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  • Yu-Ming Hsu,

    1. Laboratory Animal Center, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
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  • Hao-Jan Liang,

    1. Institute of Environmental Health, College of Public Health, National Taiwan University, Taipei, Taiwan, Republic of China
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  • Cho-Hua Wan,

    1. Graduate Institute of Molecular and Comparative Pathobiology, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
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  • Chung-Liang Chien,

    1. Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
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  • Ching-Yu Lin

    Corresponding author
    1. Institute of Environmental Health, College of Public Health, National Taiwan University, Taipei, Taiwan, Republic of China
    • Correspondence to: Ching-Yu Lin, Rm. 723, 7 F., No.17, Xuzhou Rd., Zhongzheng Dist., Taipei City 10055, Taiwan, Republic of China.E-mail: chingyulin@ntu.edu.tw

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ABSTRACT

Naphthalene is a ubiquitous environmental pollutant to which humans are exposed. Previous studies have demonstrated that naphthalene causes bronchiolar epithelial necrosis in the mouse distal airway, after parenteral administration. In this study, metabolic variations in the bronchoalveolar lavage fluid (BALF) and the lung tissues of naphthalene-treated mice and controls were examined using nuclear magnetic resonance (NMR)-based metabolomics to identify the toxic mechanism. Male ICR mice were treated with naphthalene [0, 50, 100 and 200 mg kg–1, intraperitoneally (i.p.)]. After 24 h, BALF and lung tissues were collected and prepared for 1H and J-resolved (JRES) NMR analysis after principal component analysis (PCA). PCA modeling of p-JRES spectra from the BALF, as well as hydrophilic and hydrophobic lung metabolites, enabled the high-dose group to be discriminated from the control group; increased levels of isopropanol, ethane, and acetone and lower levels of ethanol, acetate, formate, and glycerophosphocholine were detected in the BALF of mice treated with higher doses of naphthalene. Furthermore, increased isopropanol and phosphorylcholine-containing lipid levels and decreased succinate and glutamine levels were discovered in the lungs of naphthalene-exposed mice. These metabolic changes may be related to lipid peroxidation, disruptions of membrane components and imbalanced energy supply, and these results may partially explain the loss of cell membrane integrity in the airway epithelial cells of naphthalene-treated mice. We conclude that NMR-based metabolomic studies on BALF and lung tissues are a powerful tool to understand the mechanisms underlying respiratory toxicity. Copyright © 2014 John Wiley & Sons, Ltd.

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